Temperature- and composition-dependent conformational transitions of amphipathic peptide–phospholipid nanodiscs

Anada, Chiharu; Ikeda, Keisuke; Egawa, Ayako; Fujiwara, Toshimichi; Nakao, Hiroyuki; Nakano, Minoru

doi:10.1016/j.jcis.2020.12.090

Cited by 18 publications

(25 citation statements)

References 38 publications

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“…For bead i th , the non-bonded interaction is contributed by all the other beads within a cutoff radius R C . Also, the three nonbonded interaction forces F C , F R , and F D are (5) where α ij is the repulsion interaction parameter between each bead and can be estimated by the Flory−Huggins parameter χ ij with the equation (6) where χ ij represents the solubility between two kinds of DPD beads, and a larger χ ij indicates worse compatibility between two different kinds of DPD beads. For the same kind of DPD beads, α ii = 25, and χ ii = 0.γ is the friction coefficient, σ is the noise amplitude.…”

Section: Model and Simulation Methodsmentioning

confidence: 99%

“…Fan et al studied interactions between liposomes and hydrophobic nanosheets to help future nanotoxicology studies of 2D nanomaterials . Synthetic vesicles are often used for drug and gene carriers due to their cavity structure, low toxicity, and functionality. − Compared with the small molecules, the polymers provide greater mechanical strength and more functions with different chemical modifications. , Even though the polymeric vesicles have good potential for practical applications, because of blood and protein, in vivo, it is also hard to maintain a stable vesicle structure . On the other hand, the poor preparation efficiency (solid content lower than 0.1%w/w) significantly blocks its commercial application to the traditional polymer self-assembly strategy .…”

Section: Introductionmentioning

confidence: 99%

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Polymerization-Induced Self-Assembly of Comb-like Amphiphilic Copolymers into Onion-like Vesicles

Wang

et al. 2021

Macromolecules

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A multilamellar or onion-like vesicle is an enclosed structure always self-assembled by multiple polymer bilayers. Compared with the unilamellar vesicle, onion-like vesicles show more complex functionality and better structural stability, making onion-like vesicles have better and more applications in drug and gene delivery. On the other hand, polymerizationinduced self-assembly (PISA) is an improved polymer self-assembly strategy that can significantly increase preparation efficiency. Therefore, using the PISA strategy to prepare onion-like vesicles can further increase their commercial application potential. Herein, we show computer evidence that comb-like copolymers can self-assemble into the onion-like vesicle by PISA. The influence of rigidity, degree of polymerization, and structural symmetry of the macromolecular chain transfer agent (macro-CTA) on the morphology transformation is explored in our work. At the same time, we find the hollow onion-like vesicle and the solid onion-like vesicle can be synthesized by regulating the structural symmetry of macro-CTA, and the formation ways are different. Finally, we develop design guidelines of comb-like copolymers for preparing the onion-like vesicle by PISA, which can be exploited for drug and gene delivery applications.

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Section: Model and Simulation Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polymerization-Induced Self-Assembly of Comb-like Amphiphilic Copolymers into Onion-like Vesicles

Wang

et al. 2021

Macromolecules

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“…With soft matter preparation, we are heavily reliant on hydrophobic interactions, and predicting the resultant morphology of an assembly from a given molecular structure is not an easy task. , In nature, cells use phase separation behavior in the plasma membrane by multiple components to create unique shapes, such as lipid rafts and caveolae. Reports of bicelles, − cubosomes, red blood cell-like disks, , round-bottomed flasks, − and more complex formations suggest that unique complex morphologies, inaccessible with single molecules, can be achieved by co-assembly of more than one amphipathic molecule. With these ideas in mind, we focused on building up an assembly on top of another existing assembly.…”

Section: Introductionmentioning

confidence: 99%

End-Sealing of Peptide Nanotubes by Cationic Amphiphilic Polypeptides and Their Salt-Responsive Accordion-like Opening and Closing Behavior

et al. 2022

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One strategy to prepare phase-separated co-assembly is to use the existing assembly as a platform to architect structures. For this purpose, the edge of a sheet or tube-shaped molecular assembly, which is less hydrophilic than the bulk region can become a starting point to build assembly units to realize more complex structures. In this study, we succeeded in preparing rod-shaped nanocapsules with previously unachieved sealing efficiency (>99%) by fine-tuning the properties of cationic amphiphilic polypeptides to seal the ends of neutral charge nanotubes. In addition, we demonstrated the nanocapsule’s reversible responsiveness to salt. In high salt concentrations, a decrease in electrostatic repulsion between cationic polypeptides caused tearing and shrinking of the nanocapsule’s sealing dome, which resulted in an opened nanotube. On the other hand, when salt was removed, the electrostatic repulsion among the cationic peptides localizing on the edge of opened nanocapsules was recovered, and the sealing membrane swelled up like an accordion to create a distance between the peptides, resulting in the restoration of the seal.

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“…Moreover, because of their unique intrinsic targeting capabilities, sHDLs have been demonstrated to serve as versatile molecular platforms in several drug delivery applications, including the presentation of cancer neoantigens to the immune system, targeted delivery of liver X receptor agonists to arterial macrophages, and the delivery of cytotoxic cancer therapeutics through overexpressed SR-BI receptors (3)(4)(5). Therefore, many research studies have been recently carried out to understand their genesis, structural, mechanistic, and pharmacokinetic properties to tailor advanced medicinal nanodiscs for different therapeutic areas (6)(7)(8)(9)(10)(11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

“…Molecular dynamics (MD) simulations and experimental evidence have shown that in the nanodisc the lipids form a bilayer/bicelle-like structure where the amphiphilic ahelical peptides reside in the rim of the disc, shielding the hydrophobic acyl chains of PLs from aqueous surroundings and stabilizing the nanoparticles (11,(17)(18)(19). Depending on the type of apoA-I mimetic peptides and PLs, and their ratio, the overall size of nanodiscs ranges from a few to tens of nanometers based on dynamic light scattering (DLS) and electron microscopy (EM) analyses (10,20).…”

Section: Introductionmentioning

confidence: 99%

Mechanistic insights into the activation of lecithin-cholesterol acyltransferase in therapeutic nanodiscs composed of apolipoprotein A-I mimetic peptides and phospholipids

Giorgi

Niemelä

Kumpula

et al. 2022

Preprint

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The mechanistic details behind the activation of lecithin-cholesterol acyltransferase (LCAT) by apolipoprotein A-I (apoA-I) and its mimetic peptides are still enigmatic. Resolving the fundamental principles behind the LCAT activation will facilitate the design of advanced HDL-mimetic therapeutic nanodiscs for LCAT deficiencies and coronary heart disease, and for several targeted drug delivery applications. Here, we have combined coarse-grained molecular dynamics simulations with complementary experiments to gain mechanistic insight into how apoA-I mimetic peptide 22A and its variants attune LCAT activity in peptide-lipid nanodiscs. Results highlight that peptide 22A forms transient antiparallel dimers in the rim of nanodiscs. The dimerization tendency considerably decreases with the removal of C-terminal lysine K22, which has also been shown to reduce the cholesterol esterification activity of LCAT. In addition, our simulations revealed that LCAT prefers to localize to the rim of nanodiscs in a manner that shields the membrane-binding domain (MBD), αA-αA’, and the lid amino acids from the water phase, following the previous experimental evidence. Meanwhile, the location and conformation of LCAT in the rim of nanodisc are spatially more restricted when the active site covering lid of LCAT is in the open form. The average location and spatial dimensions of LCAT in its open form were highly compatible with the electron microscopy images. All peptide 22A variants studied here had a specific interaction site in the open LCAT structure flanked by the lid and MBD domain. The bound peptides showed different tendencies to form antiparallel dimers and, interestingly, the temporal binding site occupancies of the peptide variants affected their in vitro ability to promote LCAT-mediated cholesterol esterification.

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Temperature- and composition-dependent conformational transitions of amphipathic peptide–phospholipid nanodiscs

Cited by 18 publications

References 38 publications

Polymerization-Induced Self-Assembly of Comb-like Amphiphilic Copolymers into Onion-like Vesicles

Polymerization-Induced Self-Assembly of Comb-like Amphiphilic Copolymers into Onion-like Vesicles

End-Sealing of Peptide Nanotubes by Cationic Amphiphilic Polypeptides and Their Salt-Responsive Accordion-like Opening and Closing Behavior

Mechanistic insights into the activation of lecithin-cholesterol acyltransferase in therapeutic nanodiscs composed of apolipoprotein A-I mimetic peptides and phospholipids

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